Cysteine- and glycine-rich protein 3 regulates glucose homeostasis in skeletal muscle
| Autor: | Natalie Weber, Angelina Hernandez-Carretero, Samuel LaBarge, Olivia Osborn, Simon Schenk, Veronika Peterka, Nhu Y Thi Doan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism Glucose uptake Muscle Proteins Inflammation Diet High-Fat 03 medical and health sciences Mice 0302 clinical medicine Physiology (medical) Internal medicine medicine Glucose homeostasis Animals Homeostasis Hypoglycemic Agents Insulin Obesity CSRP3 Muscle Skeletal Protein Kinase C Mice Knockout Glucose Transporter Type 4 Chemistry Skeletal muscle LIM Domain Proteins Mice Inbred C57BL 030104 developmental biology Endocrinology Postprandial medicine.anatomical_structure Glucose Glycine medicine.symptom Insulin Resistance 030217 neurology & neurosurgery Cysteine Research Article |
| Popis: | Skeletal muscle is the major site of postprandial peripheral glucose uptake, but in obesity-induced insulin-resistant states insulin-stimulated glucose disposal is markedly impaired. Despite the importance of skeletal muscle in regulating glucose homeostasis, the specific transcriptional changes associated with insulin-sensitive vs. -resistant states in muscle remain to be fully elucidated. Herein, using an RNA-seq approach we identified 20 genes differentially expressed in an insulin-resistant state in skeletal muscle, including cysteine- and glycine-rich protein 3 ( Csrp3), which was highly expressed in insulin-sensitive conditions but significantly reduced in the insulin-resistant state. CSRP3 has diverse functional roles including transcriptional regulation, signal transduction, and cytoskeletal organization, but its role in glucose homeostasis has yet to be explored. Thus, we investigated the role of CSRP3 in the development of obesity-induced insulin resistance in vivo. High-fat diet-fed CSRP3 knockout (KO) mice developed impaired glucose tolerance and insulin resistance as well as increased inflammation in skeletal muscle compared with wild-type (WT) mice. CSRP3-KO mice had significantly impaired insulin signaling, decreased GLUT4 translocation to the plasma membrane, and enhanced levels of phospho-PKCα in muscle, which all contributed to reduced insulin-stimulated glucose disposal in muscle in HFD-fed KO mice compared with WT mice. CSRP3 is a highly inducible protein and its expression is acutely increased after fasting. After 24h fasting, glucose tolerance was significantly improved in WT mice, but this effect was blunted in CSRP3-KO mice. In summary, we identify a novel role for Csrp3 expression in skeletal muscle in the development of obesity-induced insulin resistance. |
| Databáze: | OpenAIRE |
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